Immunoglobulin D (IgD)- Structure and Functions
IgD is one of the five classes of immunoglobulins, which are proteins that function as antibodies in the immune system. Immunoglobulins are produced by B cells, a type of white blood cell, and can bind to specific antigens, such as bacteria, viruses, or toxins. By binding to antigens, immunoglobulins can mark them for destruction by other immune cells or neutralize their harmful effects.
IgD is a monomeric immunoglobulin, meaning that it consists of a single unit of four polypeptide chains: two identical heavy chains and two identical light chains. The heavy chains are of the delta (δ) class, which distinguishes IgD from other immunoglobulin classes. The light chains can be either kappa (κ) or lambda (λ) type, depending on the genetic rearrangement that occurs during B cell development.
The four chains are held together by disulfide bonds, which are covalent bonds between sulfur atoms. The disulfide bonds form between the heavy and light chains, as well as within each chain. The intrachain disulfide bonds divide each chain into domains, which are regions with a similar structure and function. The light chains have two domains: one variable (VL) and one constant (CL). The heavy chains have four domains: one variable (VH) and three constant (CH1, CH2, and CH3).
The variable domains of the heavy and light chains form the antigen binding site of IgD. Each IgD molecule has two antigen binding sites that can recognize the same antigen. The antigen binding site is also called the Fab (fragment antigen binding) region of IgD. The constant domains of the heavy chains form the Fc (fragment crystallizable) region of IgD, which can interact with other immune cells or molecules.
IgD can exist in two forms: membrane-bound or secreted. Membrane-bound IgD is expressed on the surface of mature B cells, along with IgM, another class of immunoglobulin. Membrane-bound IgD has an extra amino acid sequence at the C-terminal end of the CH3 domain that anchors it to the plasma membrane. It also associates with two accessory proteins called Ig-alpha and Ig-beta, which help transmit signals from IgD to the B cell.
Secreted IgD is released into the blood and mucosal secretions by a subset of B cells called IgD-secreting plasma cells. Secreted IgD does not have the extra amino acid sequence or the accessory proteins. It is a glycoprotein, meaning that it has sugar molecules attached to some of its amino acids. The sugar molecules may affect the stability and solubility of IgD.
The structure of IgD has some unique features that may influence its function. One of them is the long hinge region between the Fab and Fc regions. The hinge region is a flexible segment that allows IgD to bend and twist when binding to antigens. The hinge region also makes IgD more susceptible to proteolytic degradation by enzymes that can break down proteins.
The structure of IgD is summarized in the following diagram:
|------------------|------------------| | | | | | | | | | | VL VH | VL VH | | | | | | | | | | |------------------|------------------| | CL | CL | |------------------|------------------| | CH1 | CH1 | |------------------|------------------| | CH2 | CH2 | |------------------|------------------| | CH3 | CH3 | |------------------|------------------| | C-terminal | C-terminal | | sequence | sequence | | (membrane- | (membrane- | | bound only) | bound only) | |------------------|------------------|
IgD is an immunoglobulin that consists of two types of polypeptide chains: heavy and light. Each IgD molecule has two identical heavy chains and two identical light chains, which are linked by disulfide bonds. The heavy chains belong to the delta (δ) class, while the light chains can be either kappa (κ) or lambda (λ).
The heavy and light chains have different regions that perform different functions. The N-terminal regions of both chains are called variable regions (V), because they vary in amino acid sequence among different antibodies. The variable regions are responsible for binding to specific antigens. The C-terminal regions of both chains are called constant regions (C), because they are relatively conserved in amino acid sequence among different antibodies. The constant regions determine the class and subclass of the immunoglobulin, and also interact with other molecules and cells involved in the immune response.
The constant region of the light chain has only one domain (CL), while the constant region of the heavy chain has three domains (CH1, CH2 and CH3). The domains are separated by flexible regions called hinges, which allow the antibody to bend and adapt to different shapes of antigens. The hinge region of IgD is particularly long and susceptible to proteolytic cleavage, which may affect its stability and function.
The IgD molecule can exist in two forms: membrane-bound or secreted. The membrane-bound form is expressed on the surface of B cells, where it serves as an antigen receptor. The secreted form is found in blood and mucosal secretions, where it may have other roles in immune defense. The two forms differ only in their C-terminal ends: the membrane-bound form has a hydrophobic tail that anchors it to the lipid bilayer, while the secreted form has a hydrophilic tail that allows it to be soluble in aqueous environments. The membrane-bound form also associates with two accessory proteins called Ig-alpha and Ig-beta, which help transmit signals from the antigen binding to the B cell interior.
The following diagram shows the composition of IgD:
|-----------------|-----------------|-----------------|-----------------| | | | | | | V H | C H1 | C H2 | C H3 | | | | | | |-----------------|-----------------|-----------------|-----------------| | | | | | | V L | C L | | | | | | | | |-----------------|-----------------|-----------------|-----------------|
The antigen binding areas of IgD are the regions where the antibody can recognize and bind to a specific antigen. Antigens are foreign substances that trigger an immune response in the body. The antigen binding areas of IgD are located at the tips of the Y-shaped molecule, and consist of both light and heavy chains. Each light chain has a variable region (VL) and a constant region (CL), while each heavy chain has a variable region (VH) and three constant regions (CH1, CH2, and CH3). The variable regions of the light and heavy chains form the antigen binding site, which is unique for each antibody and can fit only one type of antigen.
The valency of IgD is the number of antigen binding sites on the antibody molecule. IgD has a valency of 2, which means it can bind to two identical antigens at the same time. This increases the specificity and affinity of the antibody-antigen interaction, and enhances the immune response. IgD can also cross-link antigens on the surface of B cells or other cells, which can trigger signaling pathways that lead to activation or inhibition of these cells.
The heavy and light chains of IgD are composed of segments called domains, which are folded into globular structures. Each domain contains about 110 amino acids and is stabilized by intrachain disulfide bonds. The domains are classified into variable (V) and constant (C) regions based on their sequence variability among different antibodies.
The variable regions are located at the N-terminal ends of the heavy and light chains and are responsible for binding to specific antigens. The variable regions of the heavy and light chains form the antigen-binding site of the antibody. Each variable region has three hypervariable or complementarity-determining regions (CDRs) that directly contact the antigen and confer specificity. The CDRs are flanked by four framework regions (FRs) that provide structural support.
The constant regions are located at the C-terminal ends of the heavy and light chains and are responsible for mediating effector functions of the antibody. The constant regions of the heavy chains determine the class or isotype of the antibody, such as IgD, IgM, IgG, IgA or IgE. The constant regions of the light chains determine the type or subtype of the light chain, such as kappa (κ) or lambda (λ). The constant regions also interact with other molecules or cells involved in immune responses, such as complement proteins, Fc receptors, or B cell receptors.
The light chains have two domains: one variable (VL) and one constant (CL). The heavy chains have four domains: one variable (VH) and three constant (CH1, CH2 and CH3). The CH1 domain is adjacent to the hinge region and is involved in binding to the light chain. The CH2 domain is involved in binding to complement proteins. The CH3 domain is involved in binding to Fc receptors on various cells.
The structure of IgD is similar to other immunoglobulins, except that it has an extra CH domain (CH4) at the C-terminal end of the heavy chain. This domain is unique to IgD and is responsible for anchoring the antibody to the membrane of B cells. It also associates with two accessory proteins called Ig-alpha and Ig-beta, which form part of the B cell receptor complex and transduce signals upon antigen binding.
The hinge region is a part of the immunoglobulin molecule that connects the Fab (antigen-binding) and Fc (effector) regions. It is composed of amino acid residues that are flexible and allow the Fab regions to move independently and adjust their orientation to bind to different antigens. The hinge region also contains disulfide bonds that link the heavy chains together and stabilize the immunoglobulin structure.
The hinge region of IgD is unique among the immunoglobulin classes. It is much longer than the hinge regions of IgG, IgA and IgE, and contains more proline residues that increase its flexibility. The hinge region of IgD also has fewer disulfide bonds than other immunoglobulins, making it more susceptible to proteolytic cleavage by enzymes. This results in the production of Fab and Fc fragments that can have different biological functions.
The long and flexible hinge region of IgD may have some advantages for its function as an antigen receptor on B cells. It may allow IgD to bind to a wider range of antigens with different shapes and sizes, and to accommodate conformational changes in antigens during binding. It may also enable IgD to interact with other molecules on the B cell surface, such as co-receptors and signaling molecules, and modulate the activation and differentiation of B cells.
However, the long and flexible hinge region of IgD may also have some disadvantages. It may make IgD more prone to degradation by proteases in the extracellular environment, reducing its stability and half-life. It may also expose IgD to unwanted interactions with other molecules, such as complement components and Fc receptors, that could interfere with its function or trigger unwanted immune responses.
The exact role of the hinge region of IgD in its structure and function is still not fully understood. More studies are needed to elucidate how the hinge region affects the antigen binding and signaling properties of IgD, and how it influences the development and regulation of B cells.
IgD is one of the five classes of immunoglobulins that are produced by B cells and play a vital role in the immune system. IgD has two main functions: as an antigen receptor on B cells and as a secreted antibody in blood and mucosal secretions.
As an antigen receptor, IgD is expressed on the surface of naive B cells, along with IgM, and binds to specific antigens that trigger the activation and differentiation of B cells into plasma cells or memory cells. This process initiates the humoral immune response, which involves the production of antibodies that can neutralize pathogens or mark them for destruction by other immune cells.
As a secreted antibody, IgD is found in low concentrations in blood serum and mucosal secretions such as saliva, tears, and bronchial fluids. The function of secreted IgD is not fully understood, but it may have a role in protecting the mucosal surfaces from infections by binding to antigens and activating innate immune cells such as basophils and mast cells. These cells can release antimicrobial factors and inflammatory mediators that can kill or inhibit the growth of pathogens.
IgD may also have a role in allergic reactions, as it can bind to allergens and trigger the release of histamine and other substances from basophils and mast cells that cause symptoms such as itching, sneezing, and wheezing.
IgD is a unique immunoglobulin that has both membrane-bound and secreted forms and performs diverse functions in the immune system. In this article, we will explore the structure and functions of IgD in more detail.
One of the main functions of IgD is to serve as an antigen receptor on the surface of B cells, which are the cells that produce antibodies. IgD is co-expressed with IgM on the membrane of naive B cells, which have not encountered their specific antigen yet. IgD and IgM have the same antigen specificity, meaning that they can bind to the same antigen.
When IgD or IgM on a B cell binds to an antigen, it triggers a series of events that lead to the activation of the B cell. The antigen-bound IgD or IgM is internalized by the B cell and processed into smaller fragments called peptides. These peptides are then presented on the surface of the B cell along with a molecule called MHC class II. This allows the B cell to interact with a helper T cell, which recognizes the peptide-MHC complex and provides signals to the B cell to proliferate and differentiate.
Depending on the type and amount of signals from the helper T cell and other factors, the B cell can differentiate into either a plasma cell or a memory B cell. A plasma cell is a specialized B cell that secretes large amounts of antibodies into the blood or other body fluids. A memory B cell is a long-lived B cell that retains the memory of the antigen and can quickly respond to it in case of a future encounter.
The differentiation of B cells also involves a process called class switching, which changes the type of antibody produced by the B cell from IgM or IgD to IgG, IgA or IgE. Class switching is mediated by a mechanism called somatic hypermutation, which introduces mutations in the variable regions of the antibody genes. This results in a diversity of antibodies with different affinities and specificities for the antigen.
By serving as an antigen receptor on B cells, IgD plays a crucial role in initiating and regulating the humoral immune response, which is the production of antibodies against foreign antigens.
The humoral immune response is the production of antibodies by B cells to neutralize and eliminate extracellular pathogens and toxins. IgD plays an important role in initiating and regulating this response by acting as an antigen receptor on the surface of naive B cells.
Naive B cells are B cells that have not encountered their specific antigen yet. They express both IgM and IgD on their surface, which have the same antigen specificity but different effector functions. IgM is a pentameric antibody that can bind to multiple antigens and activate the complement system. IgD is a monomeric antibody that has a higher affinity for antigens and can bind to low concentrations of antigens.
When IgM and IgD on a naive B cell bind to an antigen, they trigger a series of intracellular signaling events that lead to the activation of the B cell. The activated B cell then internalizes the antigen and processes it into peptides that are presented on its surface in association with MHC class II molecules. These peptides are recognized by helper T cells, which provide further signals to the B cell to proliferate and differentiate into plasma cells or memory B cells.
Plasma cells are antibody-secreting cells that produce large amounts of antibodies specific for the antigen. These antibodies circulate in the blood and mucosal secretions and bind to the antigens, marking them for destruction by phagocytes or complement. Memory B cells are long-lived cells that retain the antigen specificity and can quickly respond to a secondary exposure to the same antigen.
IgD also regulates the humoral immune response by modulating the expression of other immunoglobulin classes on B cells. IgD can induce class switching, which is the process by which a B cell changes its immunoglobulin class from IgM or IgD to IgG, IgA or IgE, depending on the type of antigen and the cytokines produced by helper T cells. Class switching allows B cells to produce antibodies with different effector functions that are more suitable for different types of pathogens.
IgD can also inhibit class switching by preventing the expression of activation-induced cytidine deaminase (AID), an enzyme that is essential for class switching. This inhibition may prevent excessive or inappropriate production of antibodies that could cause autoimmune diseases or allergic reactions.
IgD thus plays a crucial role in initiating and regulating the humoral immune response by acting as an antigen receptor on naive B cells and modulating their differentiation and class switching. By doing so, IgD helps to generate a diverse and effective antibody repertoire that can protect against various pathogens and toxins.
Although IgD is mainly expressed on the surface of B cells, a small amount of IgD is also secreted into the blood and mucosal secretions such as saliva, tears and breast milk. The function of secreted IgD is not well understood, but some studies have suggested that it may have a role in immune regulation and protection.
One possible function of secreted IgD is to modulate the activity of B cells by binding to antigens and delivering signals that either enhance or inhibit their activation. This may help to maintain a balance between tolerance and immunity, and prevent excessive or inappropriate responses. Secreted IgD may also act as a feedback mechanism to regulate the production of other immunoglobulins by B cells.
Another possible function of secreted IgD is to interact with commensal bacteria and mucosal antigens and promote their clearance or tolerance. Secreted IgD may bind to antigens that are not harmful or beneficial to the host and prevent them from triggering inflammatory responses. Secreted IgD may also help to maintain the homeostasis of the microbiota by facilitating the colonization of beneficial bacteria and inhibiting the growth of pathogenic bacteria.
A third possible function of secreted IgD is to enhance the innate immune response by activating basophils and mast cells. Secreted IgD can bind to specific receptors on these cells and trigger their degranulation and release of antimicrobial factors such as histamine, leukotrienes and cytokines. These factors can help to fight against infections, especially in the respiratory tract where IgD is abundant. Secreted IgD may also stimulate the production of IgA by B cells, which can further enhance the mucosal immunity.
In summary, secreted IgD is a minor but potentially important component of the humoral immune system that may have multiple functions in blood and mucosal secretions. More research is needed to elucidate the exact mechanisms and significance of secreted IgD in health and disease.
Basophils and mast cells are types of granulocytes that are involved in inflammatory and allergic responses. They contain granules that store various mediators, such as histamine, heparin, proteases, cytokines and chemokines. These mediators are released when the cells are activated by stimuli such as allergens, pathogens or IgE antibodies.
IgD can also bind to specific receptors on basophils and mast cells and activate them to release their granules. The receptors for IgD are called FcεRII or CD23. These receptors are different from the receptors for IgE (FcεRI), which have a higher affinity and are more widely expressed on basophils and mast cells.
The activation of basophils and mast cells by IgD is thought to have a role in immune defense against respiratory infections. IgD is present in mucosal secretions and can bind to antigens from bacteria, viruses or fungi. This can trigger the release of antimicrobial factors from basophils and mast cells, such as nitric oxide, reactive oxygen species, defensins and cathelicidins. These factors can kill or inhibit the growth of the pathogens and enhance the clearance of the infection.
The activation of basophils and mast cells by IgD may also have a role in allergic reactions. IgD can cross-link with IgE on the surface of these cells and amplify the release of inflammatory mediators. This can lead to symptoms such as itching, sneezing, wheezing, swelling and anaphylaxis. However, the exact mechanism and significance of this cross-linking is still unclear and needs further investigation.
Possible role of IgD in allergic reactions
Allergic reactions are hypersensitive immune responses to harmless substances (allergens) that trigger the production of IgE antibodies and the activation of mast cells and basophils. These cells release histamine and other inflammatory mediators that cause symptoms such as itching, sneezing, wheezing, swelling and anaphylaxis.
The role of IgD in allergic reactions is not well understood, but some studies have suggested that IgD may have both protective and pathogenic effects depending on the context.
On one hand, IgD may have a protective role by binding to basophils and mast cells and activating them to produce antimicrobial factors that participate in respiratory immune defense in humans. It also stimulates basophils to release B cell homeostatic factors that promote the survival and differentiation of B cells.
On the other hand, IgD may have a pathogenic role by enhancing the production of IgE antibodies and the activation of mast cells and basophils in response to allergens. This may lead to increased inflammation and tissue damage in allergic diseases such as asthma, rhinitis and atopic dermatitis.
Moreover, IgD may have a dual role in the development of tolerance and the outgrowing of allergies. Tolerance is the ability of the immune system to recognize and ignore harmless substances without triggering an allergic reaction. Outgrowing is the phenomenon of losing an allergic reaction over time due to repeated exposure to allergens. Some studies have shown that IgD may be involved in both processes by regulating the production of IgE antibodies and the activation of B cells.
In summary, IgD may have some role in allergic reactions, but its exact function and mechanism are still unclear and require further investigation. IgD may have both beneficial and detrimental effects on the immune system depending on the type and dose of allergen, the genetic background of the individual, and the environmental factors that influence the immune response.
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